Biopolym. Cell. 2019; 35(1):30-38.
Molecular Biomedicine
The STAT5 transcription factor in B-cells of patients with chronic lymphocytic leukemia
1Matvieieva A. S., 1Kovalevska L. M., 1Ivanivska T. S., 2Klein E., 1, 2Kashuba E. V.
  1. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022
  2. Karolinska Institutet
    Stockholm SE-171 77, Sweden


Aim. To find out the cause of inhibition of the IL2-STAT5 signaling pathway in chronic lymphocytic leukemia (CLL) cells. Methods.CLL cells were isolated from peripheral blood, using gradient centrifugation on a ficoll-verografin mixture. Expression of the STAT1-6 genes at the mRNA level was analyzed, using the Oncomine database. Expression, phosphorylation status and cellular localization of the STAT5 protein were studied by fluorescence microscopy, using specific antibodies. Results.Unlike B-cells of healthy donors, expression of the STAT5A protein was low in the patient CLL cells. As we have previously shown, the IL-2-STAT5 (JAK-STAT5) signaling pathway is inhibited in CLL cells. Now we demonstrated a low level of phosphorylation of the STAT5 protein, or a complete lack of phosphorylation in CLL cells. The STAT5A protein shows cytoplasmic localization, indicating the absence of complexes in the nucleus that activate/repress transcription of the STAT5-dependent genes. Conclusions. Inhibition of the IL-2-STAT5 pathway in CLL cells is caused by a lack of the STAT5 proteins phosphorylation and/or the absence of the active STAT5A transcription complexes in the nucleus of CLL cells.
Keywords: Chronic lymphocytic leukemia (CLL), B-peripheral blood cells, STAT5, STAT5A, STAT5B, IL2-STAT5 signaling pathway


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